Abstract This application proposes the establishment of a Center of Innovation (COIN), to be called the Pain Research, Informatics, Medical comorbidities, and Education (PRIME) Center, that builds on the successes of our existing PRIME Center, which has been supported by the Research Enhancement Award Program (REAP) since 2008 at the West Haven campus of VA Connecticut Healthcare System (VACHS). The mission and focused area of research of the PRIME Center is to study the complex interactions between pain and associated chronic conditions and behavioral health factors to develop and implement effective interventions that can reduce pain, its negative impacts on emotional and physical functioning, and overall disease burden. We will accomplish our mission by employing principles of medical informatics, behavioral science, and health services research. The strategic goals of the PRIME Center are: 1) Enact a strategic research agenda to advance scientific knowledge and to have a significant impact on improving care for Veterans with pain and associated chronic disease; 2) Foster innovative health services research outside the focused area; 3) Establish a strong infrastructure that supports mentoring and career development, including partnered, system- oriented research; and 4) Promote interdisciplinary, cross-institutional collaborations and research networks in priority areas. This plan emphasizes research that promotes implementation of an empirically informed and population based Stepped Care Model of Pain Management as the single standard of pain care. A cornerstone of this agenda is a HSR&D Collaborative Research to Enhance and Advance Transformational Excellence (CREATE) titled, Enhancing Patient Aligned Care Team (PACT) Delivered Pain Management that will promote Veteran-centered pain management and transformations in pain care in the primary care setting. Results and products will provide an improved alternative pain assessment strategy, an integrated, sustainable intervention for safe and effective opioid therapy and pain self-management, and a cohort/database for examining pain and pain management among Veterans with painful musculoskeletal conditions, the most common pain condition. Key patient care services partners and operations leaders have been engaged in developing and supporting the Center's strategic goals, objectives, and projects. Letters document support from Pain Management/Specialty Care Services, Mental Health and Primary Care Services and Clinical Operations, Analytics and Business Intelligence, and Patient Care Services, as well as the Director of VA New England Healthcare System. The infrastructure for the PRIME Center will employ several interacting Cores, including Methodology and Biostatistics, Medical Informatics, Education, Dissemination, and Implementation, and Administration and Coordination, and several Working Groups focusing on areas of research that are central to our strategic plan. The PRIME COIN will serve as a key resource to the Office of Research and Development and HSR&D in establishing and advancing an agenda of high quality health services research, with a focus on pain and pain management research.